PubMed1981
In a preliminary study, the stimulatory effect of histamine on an adenylate cyclase system in a solubilized cell-free preparation of the rat hypothalamus was established. The effect was dose dependent, and the histamine concentration required for half-maximal activation (Ka) was determined at 0.1 muM. At a 10-fold higher concentration, both chloropyramine, the classical histamine H1 antagonist, and metiamide, the selective H2-receptor blocker, partially blocked this action. Experiments carried out in hypothalamic slices showed a stimulatory effect of both the H1-agonist, 2-(2-pyridyl)-ethylamine, and the H2-antagonist, dimaprit, on adenylate cyclase in the range of histamine action. These effects could be reversed completely by the H1-antagonist, mepyramine, and the H2-receptor blocker cimetidine. In an additional study, histamine, histamine agonists and antagonists were tested on the spontaneous and the potassium-activated outflow of 3H-noradrenaline from rat hypothalamic slices. Histamine did not modify this outflow significantly, whereas the H1-agonist 2-(2-pyridyl)-ethylamine, produced a marked, dose-related increase in both the spontaneous and the potassium-stimulated release of noradrenaline. The H2-receptor blocker, cimetidine, also exerted a moderate but statistically significant stimulatory effect in this system. In combination studies, the noradrenaline-releasing action of these compounds could not he reversed by the selectively acting histaminic or antihistaminic agents, showing that this effect does not relate to the histaminic or antihistaminic property of the compound. It is becoming clear that histamine exerts a direct stimulatory effect on hypothalamic adenylate cyclase. The noradrenaline-releasing potency of some histaminic and antihistaminic agents showed that these compounds might modify the clear histamine effects through the release of other transmitter amines.